Objectives of the proposed research are to understand interaction between macromolecules at crucial steps in biochemical systems. One goal is to obtain structural knowledge of the subunit structure assembly, organization, and changes in structure induced by ligand binding in a membrane containing an acetylcholine receptor from electric fish. Electron diffraction from ordered two-dimensional lattices of this and techniques for computer-optical reconstitution of stained and unstained electron micrographs will be developed and used to obtain detailed information about a fundamental neurochemical element of synaptic transmission. High-resolution structure analysis of alpha-Bungarotoxin, a toxin from Bungaris muticinctus that blocks the acetylcholine receptor, is proposed as a means to understanding the complementary stereochemistry on the receptor. Single crystal and spectroscopic studies of trypsinogen are to give models for zymogen activation in biological systems. Similar studies of synthetases, PR-ATP synthetase and thymidylate synthetase are proposed to understand regulation, enzyme mechanism, and possibly gene repressor action also. A technique for electron microscopic examination of homogeneous chromosomal substructures is proposed as a means toward understanding the function of histones in chromosome assembly and transcription of DNA.